Effects of the 2016 CDC opioid prescription guidelines on opioid use and worker compensation case length in patients with back pain.

BACKGROUND: Narcotic consumption in the workers' compensation population contributes to prolonged case duration, worse clinical outcomes, and opioid dependence. In 2016, the CDC provided recommendations guiding clinicians on prescribing opioids to adult patients with chronic pain. The objective of our study was to evaluate a cause-and-effect relationship between narcotic consumption and worker compensation claim length before and following guideline revision. METHODS: An administration database was retrospectively queried to identify patients evaluated for spine-related workers' compensation claimants from 2011 to 2021. Data was recorded for age, sex, BMI, case length, narcotic usage, and injury location. Cases were grouped together by exam date before (2011-2016) and after (2017-2021) the 2016 CDC opioid guideline revision. RESULTS: Six hundred twenty-five patients were evaluated. Males composed 58% of the study population. From 2011 to 2016, narcotic consumption was reported in 54% of subjects versus no narcotic consumption in 46% of subjects (135 cases). From 2017 to 2021, narcotic consumption decreased to 37% (P = 0.00298). Prior to the guideline revision, mean case length was 635 days. Following CDC guideline revision, there was a significant decline in mean case length duration to 438 days (31% reduction) (P = 0.000868). CONCLUSION: This study demonstrates that following revised opioid prescription recommendations by the CDC in 2016, there was a statistically significant decline in opioid consumption and workers' compensation case length duration. Opioid use may influence prolonged worker disability and delayed return to work.

Staphylococcus aureus exacerbates dermal IL-33/ILC2 axis activation through evoking RIPK3/MLKL-mediated necroptosis of dry skin.

Atopic dermatitis (AD) is a persistent skin disease typified by symptoms of dry skin and recurrent eczema. Patients with AD are at heightened risk for Staphylococcus aureus infection. Group 2 innate lymphoid cells (ILC2s) are mainly activated by epithelial cell-derived cytokines IL-33 and involved in the pathogenesis of AD. However, little is known about the effect of skin delipidization on the epithelial cell-derived cytokines and dermal ILC2s in AD. In our study, we investigated the mechanism by which S. aureus infection modulates and exacerbates the pathogenesis of dry skin, leading to type 2 inflammation in the context of innate immunity. In vivo, we found that S. aureus infection aggravated delipidization-induced dermal IL-33 release and dermal ILC2 accumulation, which exacerbated skin inflammation. We also noticed that Il33fl/fl K14cre mice and Tlr2-/- mice exhibited attenuated skin inflammation. In vitro, treatment with necroptosis inhibitors reduced IL-33 release from S. aureus-infected keratinocytes. Mechanistically, we observed an increase in the necroptosis-associated kinases, MLKL and RIPK3, in S. aureus-infected mice, indicating that IL-33 release was associated with necroptotic cell death responses. Our results reveal that S. aureus infection-elicited keratinocyte necroptosis contributes to IL-33-mediated type 2 inflammation, which exacerbates the pathogenesis of dry skin.

Subtypes of preterm birth and the risk of postneonatal death.

OBJECTIVE: To examine the differences in postneonatal death risk among 3 clinical subtypes of preterm birth: preterm premature rupture of membranes (PROM), indicated preterm birth, and spontaneous preterm labor. STUDY DESIGN: We analyzed the 2001-2005 US linked birth/infant death (birth cohort) datasets. The preterm birth subtypes were classified using information on the birth certificate: reported PROM, induction of labor, cesarean section, and complications of pregnancy and labor. Cox proportional hazard models were used to estimate covariate-adjusted hazard ratios and 95% CIs for postneonatal death (from days 28 to 365). Estimation was given for preterm birth subtypes in a week-by-week analysis. Causes of death were analyzed by preterm birth subtype and then separately at 24-27, 28-31, and 32-36 weeks of gestation. RESULTS: For the total of 1895350 singleton preterm births who survived the neonatal period, the postneonatal mortality rate was 1.11% for preterm PROM, 0.78% for indicated preterm birth, and 0.53% for spontaneous preterm labor. Preterm PROM was associated with significantly higher risk of postneonatal death compared with spontaneous preterm labor in infants born at 27 weeks gestation or later. Similarly, indicated preterm birth was associated with a significantly higher risk of postneonatal death than spontaneous preterm labor in infants born at 25 weeks gestation or later. Preterm PROM and indicated preterm birth were associated with greater risk of death in the postneonatal period compared with spontaneous preterm labor, irrespective of the cause of death. CONCLUSION: Subtypes of preterm birth carry different risks of postneonatal mortality. Prevention of preterm-related postneonatal death may require more research into the root causes of preterm birth subtypes.

Immunomodulatory Role of Staphylococcus aureus in Atopic Dermatitis.

Staphylococcus aureus is a gram-positive bacterium commonly found on humans, and it constitutes the skin microbiota. Presence of S. aureus in healthy individuals usually does not pose any threat, as the human body is equipped with many mechanisms to prevent pathogen invasion and infection. However, colonization of S. aureus has been correlated with many healthcare-associated infections, and has been found in people with atopic diseases. In atopic dermatitis, constant fluctuations due to inflammation of the epidermal and mucosal barriers can cause structural changes and allow foreign antigens and pathogens to bypass the first line of defense of the innate system. As they persist, S. aureus can secrete various virulence factors to enhance their survival by host invasion and evasion mechanisms. In response, epithelial cells can release damage-associated molecular patterns, or alarmins such as TSLP, IL-25, IL-33, and chemokines, to recruit innate and adaptive immune cells to cause inflammation. Until recently, IL-36 had been found to play an important role in modulating atopic dermatitis. Secretion of IL-36 from keratinocytes can activate a Th2 independent pathway to trigger symptoms of allergic reaction resulting in clinical manifestations. This mini review aims to summarize the immunomodulatory roles of S. aureus virulence factors and how they contribute to the pathogenesis of atopic diseases.

Serum PBDEs and age at menarche in adolescent girls: analysis of the National Health and Nutrition Examination Survey 2003-2004.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs), widely used as flame retardants since the 1970s, have exhibited endocrine disruption in experimental studies. Tetra- to hexa-BDE congeners are estrogenic, while hepta-BDE and 6-OH-BDE-47 are antiestrogenic. Most PBDEs also have antiandrogenic activity. It is not clear, however, whether PBDEs affect human reproduction. OBJECTIVES: The analysis was designed to investigate the potential endocrine disruption of PBDEs on the age at menarche in adolescent girls. METHODS: We analyzed the data from a sample of 271 adolescent girls (age 12-19 years) in the National Health and Nutrition Examination Survey (NHANES), 2003-2004. We estimated the associations between individual and total serum BDEs (BDE-28, -47, -99, -100, -153, and -154, lipid adjusted) and mean age at menarche. We also calculated the risk ratios (RRs) and 95% confidence intervals (CI) for menarche prior to age 12 years in relation to PBDE exposure. RESULTS: The median total serum BDE concentration was 44.7ng/g lipid. Higher serum PBDE concentrations were associated with slightly earlier ages at menarche. Each natural log unit of total BDEs was related to a change of -0.10 (95% CI: -0.33, 0.13) years of age at menarche and a RR of 1.60 (95% CI: 1.12, 2.28) for experiencing menarche before 12 years of age, after adjustment for potential confounders. CONCLUSION: These data suggest high concentrations of serum PBDEs during adolescence are associated with a younger age of menarche.

A duplex quantitative polymerase chain reaction assay based on quantification of alpha-methylacyl-CoA racemase transcripts and prostate cancer antigen 3 in urine sediments improved diagnostic accuracy for prostate cancer.

PURPOSE: Most men with increased serum prostate specific antigen and negative biopsy require repeat biopsy because of the lack of a sensitive and specific prostate cancer detection test. In this study we evaluated the diagnostic potential of a duplex assay for prostate cancer by quantifying transcript levels of alpha-methylacyl-CoA racemase and prostate cancer antigen 3 in urine sediments following prostatic massage. MATERIALS AND METHODS: Urine sediments from 92 patients, 43 with and 49 without prostate cancer, were collected after digital rectal examination. Transcript levels of AMACR, PCA3 and PSA in total RNA isolated from these samples were determined by absolute quantitative real-time polymerase chain reaction. AMACR and PCA3 scores were obtained by normalizing the transcript level to that of prostate specific antigen for each sample and multiplying by 100. RESULTS: AMACR (p = 0.006) and PCA3 (p = 0.014) scores, but not serum prostate specific antigen (p = 0.306), distinguished specimens from patients with prostate cancer from specimens from patients without prostate cancer, and ROC analysis established the diagnostic cutoff scores for the AMACR and PCA3 tests at 10.7 and 19.9, respectively. As determined from these cutoff scores the AMACR test had 70% (95% CI 56-83) sensitivity and 71% (95% CI 59-84) specificity, whereas the PCA3 test had 72% (95% CI 59-85) sensitivity and 59% (95% CI 45-73) specificity for prostate cancer detection. The combined use of AMACR and PCA3 scores in a dual marker test increased sensitivity to 81% (95% CI 70-93) and specificity to 84% (95% CI 73-94). CONCLUSIONS: Urinary AMACR and PCA3 tests were superior to a serum prostate specific antigen test for detecting prostate cancer. Their combined use in a dual marker test further improved sensitivity and accuracy, and could serve as a surveillance test after repeat negative prostate biopsies.

Thyroid hormones in relation to lead, mercury, and cadmium exposure in the National Health and Nutrition Examination Survey, 2007-2008.

BACKGROUND: Heavy metals, such as lead (Pb), mercury (Hg), and cadmium (Cd), are known toxicants, but their associations with the thyroid axis have not been well quantified at U.S. background levels. OBJECTIVES: We investigated the relationships between thyroid hormones (total and free thyroxine [TT4 and FT4], total and free triiodothyronine [TT3 and FT3], thyroid-stimulating hormone [TSH], and thyroglobulin [Tg]) and levels of Pb, Hg, and Cd in blood and Cd in urine. METHODS: We separately analyzed a sample of 1,109 adolescents (12-19 years of age) and a sample of 4,409 adults from the U.S. National Health and Nutrition Examination Survey (NHANES) 2007-2008. We estimated associations after adjusting for age, sex, race, urinary iodine, body mass index, and serum cotinine. RESULTS: The geometric mean (GM) levels of blood Pb (BPb), total Hg, and Cd were 0.81 µg/dL, 0.47 µg/L, and 0.21 µg/L in adolescents and 1.43 µg/dL, 0.96 µg/L, and 0.38 µg/L in adults, respectively. The GMs of urinary Cd were 0.07 and 0.25 µg/g creatinine in adolescents and adults, respectively. No consistent pattern of metal and thyroid hormone associations was observed in adolescents. In adults, blood Hg was inversely related to TT4, TT3, and FT3 and urinary Cd was positively associated with TT4, TT3, FT3, and Tg, but there were no associations with Pb. Associations were relatively weak at an individual level, with about 1-4% change in thyroid hormones per interquartile range increase in Hg or Cd. CONCLUSIONS: Our analysis suggests an inverse association between Hg exposure and thyroid hormones, and a positive association between Cd exposure and thyroid hormones in adults.

α-Methylacyl-CoA racemase spliced variants and their expression in normal and malignant prostate tissues.

OBJECTIVES: To evaluate the possibility of using α-methylacyl-CoA racemase (AMACR) variants to improve the specificity of prostate cancer (CaP) detection. AMACR has been used as a diagnostic biomarker for CaP and is now a standard biomarker for needle biopsy specimens with ambiguous lesions. METHODS: We used in silico analysis and molecular cloning to discover new AMACR variants and quantitative reverse transcription-polymerase chain reaction (RT-PCR) to measure the transcript levels of AMACR and its variants in 4 prostate cell lines and in 23 pairs of CaP and adjacent normal tissue. RESULTS: We found 4 novel variants, IAs, IBL, IBLd, and IBLi. Transcript levels of most AMACR variants were significantly upregulated in CaP compared with its adjacent normal counterparts. A variants, the functional variants based on bioinformatic analysis, showed levels of transcript expression in CaP in this order: IA≫IAd=IIA≫IIAs>IAs. In contrast, the expression of the B variants, which appear to be nonfunctional due to the absence of exon 3, was lower than that of the A variants. IB was the most abundant form of B variant; and expression of IIB was negligible. More important, the difference between levels of variant IA, IAd, IIA, IIAs, IB, and IBLi in CaP and normal tissue was significantly higher than the difference in levels of total AMACR. CONCLUSIONS: Our data suggest that AMACR variants have better power than total AMACR in discriminating between CaP and adjacent normal tissue. These findings may be useful for the development of future diagnostic assays.